A Publication
of Reliable Methods
for the Preparation
of Organic Compounds
Annual Volume
Org. Synth. 1970, 50, 104
DOI: 10.15227/orgsyn.050.0104
Submitted by E. Jones1 and I. M. Moodie.
Checked by E. J. Corey and Joel I. Shulman.
1. Procedure
A 3-l. three-necked flask fitted with a mechanical stirrer, a 600-ml. dropping funnel, and filled with dry nitrogen is charged with 500 ml. of tetrahydrofuran (distilled from lithium aluminum hydride; see Org. Synth., Coll. Vol. 5, 976 (1973) for warning concerning the purification of tetrahydrofuran) and 56 g. (53 ml., 0.67 mole) of thiophene. This mixture is stirred under nitrogen and cooled to −40° with an acetone–dry ice bath while 490 ml. (0.662 mole) of 1.35 M n-butyllithium in pentane (Note 1) and (Note 2) is added over a 5-minute period via the dropping funnel. The temperature of the mixture is held between −30° and −20° for 1 hour, then lowered to −70° by the addition of dry ice to the bath. Powdered sulfur crystals (20.4 g., 0.638 g.-atom) are added in one aliquot to the stirred mixture. After 30 minutes the temperature is allowed to rise to −10°, whereupon the yellow solution is carefully poured into 1 l. of rapidly stirred ice water, dissolving the lithium thiolate and destroying any unreacted 2-thienyllithium. The pentane layer is extracted with three 100-ml. portions of water. These aqueous extracts are combined with the aqueous layer, and the whole is chilled and carefully acidified with 4 N sulfuric acid (Note 3). This aqueous phase is immediately extracted with three 200-ml. portions of diethyl ether (Note 4). The combined ether extracts are washed twice with 100-ml. portions of water to remove acid and remaining tetrahydrofuran and dried over anhydrous sodium sulfate. After removal of ether, the residual, golden-brown oil is purified by distillation at reduced pressure. The portion boiling at 53–56° (5 mm.) is collected, yielding 49.5–53.5 g. (65–70%) of 2-thiophenethiol as a yellow oil, n25D 1.6110.
2. Notes
1. The checkers obtained n-butyllithium from the Foote Mineral Co., Exton, Pennsylvania. The concentration of n-butyllithium was determined by the method of Gilman and Haubein.2 This reagent is conveniently transferred to a precalibrated addition funnel under nitrogen pressure, through a short length of inert (e.g., Teflon) tubing.
2. The submitters employed n-butyllithium prepared by the method of Jones and Gilman.3 The n-butyllithium solution so prepared was filtered to remove finely divided lithium, using an apparatus previously described.4
3. The general procedure is similar to that described by Gronowitz5 in the preparation of 3-thiophenethiol, the principal differences being the use of tetrahydrofuranpentane solvent and the omission of a 10% potassium hydroxide extraction before acidification with sulfuric acid. This omission leads to higher yields of thiol.
4. Undue delay in the ether extraction of the thiol has been found to result in reduced yields.
3. Discussion
Houff and Schuetz6 have prepared 2-thiophenethiol by two different routes. One involves the sulfurization of 2-thienylmagnesium bromide followed by acidification, giving the thiol; the other method is an in situ reduction of 2-thienylsulfonyl chloride with zinc dust and sulfuric acid. Gronowitz5 has prepared the isomeric 3-thiophenethiol by sulfurization of 3-thienyllithium, which was obtained by metalation of 3-bromothiophene with n-butyllithium.
This method is based on the known reactivity of the 2-position of thiophene; the desired 2-thiophenethiol may be prepared in good yield by direct substitution of thiophene. 2-Chloro-5-thiophenethiol may also be prepared by this method in 59% yield from 2-chlorothiophene.7
Direct substitution in the 3-position of the thiophene ring is difficult and can be achieved only by activation of this reaction site. Thus, the isomeric 3-thiophenethiol may be prepared by this general method starting with a 3-halogenothiophene. For example, 3-thiophenethiol may be obtained from 3-bromothiophene in 63% yield.5
The procedure outlined above also offers a general method for the synthesis of alkyl and aryl thiols starting from the appropriate halides. Thus, thiophenol may be obtained in 62% yield by lithiation and sulfurization of bromobenzene.8
This preparation is referenced from:

References and Notes
  1. Work done at the former Arthur D. Little Research Inst., Inveresk Gate, Musselburgh, Midlothian, Scotland.
  2. H. Gilman and A. H. Haubein, J. Am. Chem. Soc., 66, 1515 (1944).
  3. R. G. Jones and H. Gilman, Org. React., 6, 339–366 (1951).
  4. H. Gilman, W. Langham, and F. W. Moore, J. Am. Chem. Soc., 62, 2327 (1940).
  5. S. Gronowitz and R. Hakansson, Ark. Kemi, 16, 309 (1960).
  6. W. H. Houff and R. D. Schuetz, J. Am. Chem. Soc., 75, 6316 (1953).
  7. E. Jones and I. M. Moodie, Tetrahedron, 21, 2413 (1965).
  8. H. Gilman and L. Fullhart, J. Am. Chem. Soc., 71, 1478 (1949).

Chemical Abstracts Nomenclature (Collective Index Number);
(Registry Number)

sulfuric acid (7664-93-9)

diethyl ether (60-29-7)

sodium sulfate (7757-82-6)

nitrogen (7727-37-9)

sulfur (7704-34-9)

potassium hydroxide (1310-58-3)

zinc (7440-66-6)

bromobenzene (108-86-1)

Pentane (109-66-0)

Thiophenol (108-98-5)

Thiophene (110-02-1)

lithium (7439-93-2)

n-butyllithium (109-72-8)

Tetrahydrofuran (109-99-9)

lithium aluminum hydride (16853-85-3)

2-thiophenethiol (7774-74-5)

2-thienylmagnesium bromide

3-Bromothiophene (872-31-1)


2-thienylsulfonyl chloride (16629-19-9)



2-chlorothiophene (96-43-5)